Inflammatory bowel diseases (IBD) comprising Crohn's disease and ulcerative colitis are inflammatory conditions of the colon and/or the small intestine. Symptoms may overlap with other forms of chronic intestinal inflammatory conditions such as collagenous-, lymphocytic-, ischemic-, diversion- and indeterminate colitis and Behçet's disease. The exact etiology of these diseases is believed to be multifactorial but is to date still undefined (Gastroenterology, Vol 150, No 6 May 2011, 1701-1846). Therefore, current treatment aims at dampening the ongoing inflammation and is based on symptoms and presence of lesions. It is clear that new and efficient therapies for IBD with a minimum of side effects are of great interest.
Metallothioneins are cysteine rich zinc binding proteins which play a role in different cellular processes such as zinc homeostasis, oxygen radical scavenging, cell proliferation and apoptosis. They are considered to be acute phase proteins due to their rapid induction by different stimuli, including inflammation (Inoue et al. 2009).
M. Lynes (US 2003/0007973) indicated that an anti-metallothionein antibody is particularly useful to stimulate the immune response in a subject undergoing irradiation or chemotherapy, autoimmune subjects, subjects exposed to immunosuppressive agents, neonates and subjects having undergone transplantation.
Waeytens et al. (2009) review the role of metallothioneins in IBD and conclude that there is a deviant metallothionein expression in IBD but that the role of these proteins during disease is not clear.
Tran et al. (2007) and Oz et al. (2005) investigated the effect of the presence or absence of metallothioneins via metallothionein knock-out mice but could not observe a significant and beneficial effect of the absence of metallothioneins.
Devisscher et al. (2011; abstract) describe that metallothioneins have been proposed to have a role in the pathogenesis of IBD and conclude that the low metallothionein profile in IBD patients may point to a hypoxia-driven adaptive response in the course of gut inflammation.
Taken together, it remains unclear whether a reduction of metallothionein might have a beneficial role during IBD. The aberrant expression levels in IBD patients and their upregulation during inflammation (De et al. 1990; Laukens et al. 2009)), even suggest a protective effect of metallothionein during intestinal inflammation. The present invention surprisingly demonstrates that administration of antagonists targeting metallothionein, even targeting solely secreted metallothioneins by use of antibodies, results in a significant therapeutic effect of intestinal inflammation.